Multi-well test plates, also called micro-titer plates or micro-titer test plates, are well-known and frequently used for assays involving biological or biochemical materials. Micro-titer test plates have been described in numerous patents, including, e.g., U.S. Pat. Nos. 4,948,442; 3,540,856; 3,540,857; 3,540,858; 4,304,865; 4,948,564; 5,620,663; 5,464,541; and 5,264,184; International Publication Nos. WO 97/41955 and WO 95/22406; and European Patent Nos. 645 187 and 98 534.
Selected wells in the micro-titer test plate can be used to incubate respective microcultures or to separate biological or biochemical material followed by further processing to harvest the material. Each well typically includes a filter so that, upon application of a vacuum to one side of the plate, fluid in each well is expressed through the filter leaving solids, such as bacteria and the like, entrapped in the well. The filter may also act as a membrane such that certain materials in the test specimen are selectively bonded or otherwise retained in the filter. The retained material may thereafter be harvested by means of a further solvent. The liquid expressed from the individual wells through the filter may be collected in a common collection vessel in case the liquid is not needed for further processing or alternatively, the liquid from the individual wells may be collected in individual collection containers as disclosed in U.S. Pat. No. 5,464,541 and European Patent No. 98 534.
Until recently, micro-titer plates have been used that conform to a standardized size of about 85.47 millimeters (mm) by 127.76 mm having twelve (12) rows of eight (8) wells each. Many different pieces of expensive automation equipment have been designed to this standard. However, there is now a desire to increase the productivity of such automatic sampling. To do so cost effectively, it may be desirable to design equipment based on the size of conventional micro-titer plates, but that includes an increased number of wells. This would require minimal changes in the automation equipment.
Various methods are used to produce the standard micro-titer plates having 96 wells. For example, the plates may be manufactured as multi-layer structures including a single sheet of filter material to cover the bottom apertures of all the wells, the filtration material being bonded to the periphery of one or more of the well apertures. Such a structure may, however, suffer from a problem called “cross-talk” in which fluid from adjacent wells mingles within the filter material through for example capillary action, gravity or application of pressure.
As disclosed in U.S. Pat. No. 4,304,865, a micro-titer, multi-layer plate includes a substantially rigid culture tray provided with wells having upstanding edges or rims bounding the wider openings to the wells. A mating harvester tray is used in combination with the culture tray to essentially die cut filters for each well from a single sheet of filter material. This technique of cutting the filter sheet while it overlays the wells has the disadvantage that dust formed during the cutting operation can get trapped between the walls of the well and the filter medium that may cause poor separation performance.
Another approach to the problem of cross-talk is described in U.S. Pat. No. 4,948,442 in which the wells of a culture tray and harvester tray are welded together with a filter sheet located between the two trays. This method, however, still does not completely solve the problem of cross talk. In particular, welding of the wells may not be sufficient to avoid capillary action to cause mingling of fluids from adjacent wells. Moreover, cross-talk may be even more enhanced with micro-titer plates that have a high number of wells per unit area.
U.S. Patent Application 2002/0155034 A1 describes a micro-titer plate and a well-less filtration device that addresses many of the issues discussed above. These plates and devices use a Solid Phase Extraction (SPE) medium to provide the desired separation of analytes. Although the devices are successful in addressing cross-talk between wells, the plates and well-less filtration devices can present issues in manufacturability.